A Comparative Study: Cardioprotective Effects of High-Intensity Interval Training Versus Ischaemic Preconditioning in Rat Myocardial Ischaemia-Reperfusion.

(1) Background: Years of research have identified ischemic preconditioning (IPC) as a crucial endogenous protective mechanism against myocardial ischemia-reperfusion injury, enhancing the myocardial cell's tolerance to subsequent ischemic damage. High-intensity interval training (HIIT) is promoted by athletes because it reduces exercise duration and improves metabolic response and cardiopulmonary function. Our objective was to evaluate and compare whether HIIT and IPC could reduce myocardial ischemia and reperfusion injury in rats. (2) Methods: Male Sprague-Dawley rats were divided into four groups: sham surgery, coronary artery occlusion (CAO), high-intensity interval training (HIIT), and ischemic preconditioning (IPC). The CAO, HIIT, and IPC groups experienced 40 min of coronary artery occlusion followed by 3 h of reperfusion to induce myocardial ischemia-reperfusion injury. Subsequently, the rats were sacrificed, and blood samples along with cardiac tissues were examined. The HIIT group received 4 weeks of training before surgery, and the IPC group underwent preconditioning before the ischemia-reperfusion procedure. (3) Results: The HIIT and IPC interventions significantly reduced the extent of the myocardial infarction size and the levels of serum troponin I and lactate dehydrogenase. Through these two interventions, serum pro-inflammatory cytokines, including TNF-α, IL-1ß, and IL-6, were significantly decreased, while the anti-inflammatory cytokine IL-10 was increased. Furthermore, the expression of pro-apoptotic proteins PTEN, caspase-3, TNF-α, and Bax in the myocardium was reduced, and the expression of anti-apoptotic B-cell lymphoma 2 (Bcl-2) was increased, ultimately reducing cellular apoptosis in the myocardium. In conclusion, both HIIT and IPC demonstrated effective strategies with potential for mitigating myocardial ischemia-reperfusion injury for the heart.

Effect of Lactobacillus plantarum PS128 on neuromuscular efficiency after a half-marathon.

Introduction: Lactobacillus plantarum PS128 (PS128) could be considered an antioxidant supplement to reduce muscle fatigue and improve exercise capacity recovery after vigorous exercise. Purpose: The purpose of this study is to investigate the effect of PS128 on muscle fatigue and electromyography (EMG) activity after a half-marathon (HM). Methods: The experimental design used a repeated-measures design with a double-blind approach. The participants either took two capsules of PS128 for 4 weeks as the PS128 group (PSG, n = 8) or took two capsules of a placebo for 4 weeks as the placebo group (PLG, n = 8) to ensure counterbalancing. The time points of the maximal voluntary isometric contraction (MVIC) and EMG activity test were set before probiotics were taken (baseline), 48 h before HM (Pre), and immediately at 0 h, 3 h, 24 h, 48 h, 72 h, and 96 h after HM. Results: EMG activity included median power frequency (MDF), integrated EMG (iEMG), and neuromuscular efficiency (peak torque/iEMG). The MVICs of knee extensors, analyzed by using an isokinetic dynamometer, showed a decrease from the Pre to 0 h (p = 0.0001), 3 h (p < 0.0001), 24 h (p < 0.0001), 48 h (p < 0.0001), 72 h (p = 0.0002), and 96 h (p = 0.0408) time points in the PLG. Sidak's multiple comparisons tests showed that the PLG was significantly lower than the PSG at 0 h (p = 0.0173), 3 h (p < 0.0001), 24 h (p < 0.0001), 48 h (p < 0.0001), 72 h (p < 0.0001), and 96 h (p = 0.0004) time points. The MDF of vastus medialis oblique (VMO) in the PLG was significantly decreased 24 h after HM and significantly lower than that in the PSG at all times points after HM. The iEMG of VMO in the PLG was significantly decreased 48 h after HM and significantly lower than that in the PSG at 0 h, 3 h, 24 h, 48 h, and 72 h after HM. Conclusion: The PS128 supplementation may prevent the decrease in MDF, iEMG, and peak torque after vigorous exercise. Recreational runners may consider implementing a probiotic supplementation regimen as a potential strategy to mitigate muscle fatigue following HM.

Effectiveness of a Water Intake Program at the Workplace in Physical and Mental Health Outcomes.

INTRODUCTION: Adequate water intake is a low-cost and effectively non-invasive strategy for individual health outcomes. We aimed to demonstrate the efficacy of water intake intervention in intensive-labor and static-type workplaces. METHOD: Smart drinking cups were provided to the participants, and a built-in application (App) associated with the cup was downloaded on their phones. The App collected and recorded the amount of drinking water consumed by the participants set reminders for drinking water and drinking water health education information. We assessed the data, including the amount of and time interval between water intake, sedentary time, the degree of physical and psychological importance of oneself, self-satisfaction, and physical fitness. RESULTS: After the intervention, water intake in the two companies significantly increased during the reminder period compared with the non-reminder period. A significant increase was noted in week 3 in the amount of water intake by the participants after using the App, and the total sedentary time considerably decreased. Furthermore, the interval between water consumption decreased compared with the preintervention interval. The systolic and diastolic blood pressure decreased in the participants working at the static-type and intensive-labor workplaces after the intervention, respectively. The participants ' lower limb muscle performance also improved significantly, and the emphasis on self-care was significantly improved. CONCLUSIONS: The health-promoting effects of the water intake wellness intervention were akin to the butterfly effect. Besides significantly increasing water intake, the intervention improved other health behaviors, thereby benefiting physical and mental health. Hence, promoting water consumption in workplaces till it becomes a habit may benefit the employees.

Magnolol reduces myocardial injury induced by renal ischemia and reperfusion.

BACKGROUND: Magnolol is a component of the bark of Magnolia officinalis, which is a traditional herbal remedy used in China. In this study, we investigated whether magnolol can reduce myocardial injury induced by renal ischemia and reperfusion (I/R). METHODS: Renal I/R was elicited by a 60-minute occlusion of the bilateral renal arteries and a 24-hour reperfusion in Sprague-Dawley rats. Magnolol was administered intravenously 10 minutes before renal I/R to evaluate its effects on myocardial injury induced by renal I/R. RESULTS: Renal I/R significantly increased the serum levels of creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and cardiac troponin I and caused myocardial damage. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive nuclei and caspase-3 activation was significantly increased in the myocardium, indicating increase of apoptosis. Echocardiography revealed left ventricular dysfunction, as evidenced by reduction of left ventricular ejection fraction and left ventricular fractional shortening. Furthermore, serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6 were significantly elevated, while the IL-10 level was suppressed. However, intravenously, pretreatment with magnolol at doses of 0.003 and 0.006 mg/kg 10 minutes before renal I/R significantly prevented the increases of CPK, LDH, and cardiac troponin I levels, as well as the histological damage and the apoptosis in the myocardium. Echocardiography showed significant improvement of left ventricular function. Furthermore, the increases in TNF-α, IL-1ß, and IL-6 and the decrease in IL-10 were significantly limited, while Bcl-2 was increased and Bax was decreased in the myocardium. Phosphorylation of Akt and extracellular signal-regulated kinases 1 and 2 was increased, while phosphorylation of p38 and c-Jun N-terminal kinase was reduced. CONCLUSION: Magnolol reduces myocardial injury induced by renal I/R. The underlying mechanisms for this effect might be related to modulation of the production of pro- and anti-inflammatory cytokines and the limiting of apoptosis.

Effects of swimming training on myocardial protection in rats.

Swimming is important for promoting and maintaining health, as it can increase the efficiency of the cardiovascular system and decrease the occurrence of cardiovascular diseases. The objective of the present study was to examine whether swimming training could decrease myocardial injury in rats caused by myocardial ischemia/reperfusion (I/R). Sprague-Dawley rats were randomized into four groups, namely the Sham, coronary artery occlusion, swimming training and ischemic preconditioning (IPC) groups. Myocardial I/R was induced in anesthetized male Sprague-Dawley rats by a 40-min occlusion followed by a 3-h reperfusion of the left anterior descending coronary artery. The rats were sacrificed after surgery and their hearts were examined. The results demonstrated that the number of TUNEL-positive nuclei and degree of caspase-3 activation were both significantly increased in the myocardium following myocardial I/R in rats, indicating increased cardiomyocyte apoptosis. On the other hand, swimming training decreased the serum levels of creatine phosphokinase, lactate dehydrogenase and cardiac troponin I, and was associated with reduced histological damage and myocardial infarct size. Furthermore, swimming training also reduced TNF-α levels, caspase-3 activation and enhanced Bcl-2 activation, which decreased the number of apoptotic cells in the myocardium. The findings of the present study showed that swimming training and IPC could similarly decrease myocardial injury following myocardial I/R, and may therefore be used as exercise training to effectively prevent myocardial injury.

Effect of Daily Oral Lactobacillus plantarum PS128 on Exercise Capacity Recovery after a Half-Marathon.

A half-marathon (HM) is a vigorous high-intensity exercise, which could induce lower extremity musculoskeletal injury risks for recreational runners. They usually consume nonsteroidal anti-inflammatory drugs (NSAIDs) in order to shorten their return to play but ignore the side effects, such as peptic ulcers and renal and vascular disorders. Lactobacillus plantarum PS128 (PS128) could improve inflammation and oxidative stress by modulating the gut microbiota, thus potentially improving muscle damage and recovery. However, few studies have addressed the PS128 exercise capacity recovery 96 h after HM. Thus, this study aimed to investigate the effect of PS128 on exercise capacity and physiological adaptation after HM. A double-blind, randomized, placebo-controlled, counterbalanced, crossover trial was used for the experiment. HM was conducted at the beginning and end of the 4-week nutritional supplement administration. Eight recreational runners took two capsules (3 × 1010 CFU/capsule) of PS128 each morning and evening before meals for 4 weeks as the PS128 treatment (LT), or they took two capsules of placebo for 4 weeks as the placebo treatment (PT). In both treatments, an exercise capacity test (lower extremity muscle strength, anaerobic power, lower extremity explosive force, and aerobic capacity) and blood test (muscle fatigue, muscle damage, oxidative stress, and renal injury) were performed before the administration of the nutritional supplement (baseline), 48 h before HM (pre), and 0 h (0 h post), 3 h (3 h post), 24 h (24 h post), 48 h (48 h post), 72 h (72 h post), and 96 h (96 h post) after HM. There was no significant difference in the total duration of HM between PT and LT, but PT was found to be significantly higher than LT at Stage 4 (15,751-21,000 m) of HM (3394 ± 727 s vs. 2778 ± 551 s, p = 0.02). The lower extremity muscle strength measured using an isokinetic dynamometer in PT was significantly lower than that in LT at 72 h after HM. The lower extremity explosive force from the countermovement jump (CMJ) in PT was significantly decreased compared to 24 h prior. There was no significant difference between anaerobic power and aerobic capacity between the two treatments after HM. After HM, LT had lower muscle damage indices, such as myoglobin (3 h post-PT vs. -LT: 190.6 ± 118 ng/mL vs. 91.7 ± 68.6 ng/mL, p < 0.0001) and creatine phosphokinase (24 h post-PT vs. -LT: 875.8 ± 572.3 IU/L vs. 401 ± 295.7 IU/L, p < 0.0001). Blood urea nitrogen recovered in 24 h (24 h pre- vs. post-LT, p > 0.05) and higher superoxide dismutase was found in LT (96 h post-PT vs. -LT: 0.267 ± 0.088 U/mL vs. 0.462 ± 0.122 U/mL, p < 0.0001). In conclusion, PS128 supplementation was associated with an improvement in muscle damage, renal damage, and oxidative stress caused by HM through microbiota modulation and related metabolites but not in exercise capacity.

The Effects of Sleep Quality and Resilience on Perceived Stress, Dietary Behaviors, and Alcohol Misuse: A Mediation-Moderation Analysis of Higher Education Students from Asia, Europe, and North America during the COVID-19 Pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has increased the already high levels of stress that higher education students experience. Stress influences health behaviors, including those related to dietary behaviors, alcohol, and sleep; yet the effects of stress can be mitigated by resilience. To date, past research studying the connections between dietary behaviors, alcohol misuse, sleep, and resilience commonly investigated singular relationships between two of the constructs. The aim of the current study was to explore the relationships between these constructs in a more holistic manner using mediation and moderation analyses. METHODS: Higher education students from China, Ireland, Malaysia, South Korea, Taiwan, the Netherlands, and the United States were enrolled in a cross-sectional study from April to May 2020, which was during the beginning of the COVID-19 pandemic for most participants. An online survey, using validated tools, was distributed to assess perceived stress, dietary behaviors, alcohol misuse, sleep quality and duration, and resilience. RESULTS: 2254 students completed the study. Results indicated that sleep quality mediated the relationship between perceived stress and dietary behaviors as well as the relationship between perceived stress and alcohol misuse. Further, increased resilience reduced the strength of the relationship between perceived stress and dietary behaviors but not alcohol misuse. CONCLUSION: Based on these results, higher education students are likely to benefit from sleep education and resilience training, especially during stressful events.

Health Behaviors of Higher Education Students from 7 Countries: Poorer Sleep Quality during the COVID-19 Pandemic Predicts Higher Dietary Risk.

Health behaviors of higher education students can be negatively influenced by stressful events. The global COVID-19 pandemic presents a unique opportunity to characterize and compare health behaviors across multiple countries and to examine how these behaviors are shaped by the pandemic experience. Undergraduate and graduate students enrolled in universities in China, Ireland, Malaysia, South Korea, Taiwan, the Netherlands and the United States (USA) were recruited into this cross-sectional study. Eligible students filled out an online survey comprised of validated tools for assessing sleep quality and duration, dietary risk, alcohol misuse and physical activity between late April and the end of May 2020. Health behaviors were fairly consistent across countries, and all countries reported poor sleep quality. However, during the survey period, the COVID-19 pandemic influenced the health behaviors of students in European countries and the USA more negatively than Asian countries, which could be attributed to the differences in pandemic time course and caseloads. Students who experienced a decline in sleep quality during the COVID-19 pandemic had higher dietary risk scores than students who did not experience a change in sleep quality (p = 0.001). Improved sleep quality was associated with less sitting time (p = 0.010). Addressing sleep issues among higher education students is a pressing concern, especially during stressful events. These results support the importance of making education and behavior-based sleep programming available for higher education students in order to benefit students' overall health.

Increased Resilience Weakens the Relationship between Perceived Stress and Anxiety on Sleep Quality: A Moderated Mediation Analysis of Higher Education Students from 7 Countries.

High levels of perceived stress and anxiety among university students are a global concern and are known to negatively influence sleep. However, few studies have explored how stress response styles, like psychological resilience and rumination, might alter these relationships. Using validated tools, perceived stress, anxiety, stress response styles, and sleep behaviors of undergraduate and graduate students from seven countries during the height of the COVID-19 pandemic were characterized in order to examine the relationships between these factors using mediation and moderation analyses. Students enrolled in universities in China, Ireland, Malaysia, Taiwan, South Korea, the Netherlands, and the United States were recruited in May 2020. A total of 2254 students completed this cross-sectional study. Perceived stress and anxiety were negatively associated with sleep quality through the mediation of rumination. Increased psychological resilience weakened the relationships between perceived stress and anxiety on sleep quality. The majority of students reported that COVID-19 negatively influenced their mental health and sleep quality but not sleep duration. Based on these results, university students would likely benefit from sleep education and mental health promotion programs that include trainings to increase psychological resilience and reduce rumination, particularly during times of increased stress.

Magnolol Reduces Renal Ischemia and Reperfusion Injury via Inhibition of Apoptosis.

Magnolol, a constituent of the bark of Magnolia officinalis, has been reported to decrease myocardial stunning and infarct size. In this study, we investigated whether magnolol can reduce renal ischemia and reperfusion (I/R) injury. Renal I/R, induced by a 60-min occlusion of bilateral renal arteries and a 24-h reperfusion, significantly increased blood urea nitrogen (BUN) and creatinine levels, and caused histological damage to the kidneys of rats. Apoptosis, as evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and caspase-3 activation, was significantly increased in the kidneys. Furthermore, serum levels of tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were significantly elevated, while the interleukin-10 (IL-10) level was suppressed. However, intravenous pretreatment with magnolol at doses of 0.003[Formula: see text]mg/kg and 0.006[Formula: see text]mg/kg 10[Formula: see text]min before renal I/R significantly limited the increases of BUN, creatinine, the histological damage, and apoptosis in the kidneys. The increases in TNF-[Formula: see text], IL-1ß, and IL-6, and the decrease in IL-10 were also significantly inhibited. Additionally, magnolol increased Bcl-2 and decreased Bax in the kidneys. Phosphorylation of the prosurvival kinases, including Akt and extracellular signal-regulated kinases 1 and 2 (ERK1/2), was elevated, while phosphorylation of the pro-apoptotic mitogen-activated protein kinases, including p38 and c-Jun N-terminal kinase (JNK), was suppressed. In conclusion, magnolol reduces renal I/R injury. The underlying mechanisms for this effect might be related to the prevention of apoptosis, possibly via the inhibition of both extrinsic and intrinsic apoptotic pathways, including the reduction of TNF-[Formula: see text] production and the modulation of pro- and anti-apoptotic signaling elements.

Baicalein Attenuates Lung Injury Induced by Myocardial Ischemia and Reperfusion.

Baicalein is an active component of Scutellaria baicalensis Georgi, which has traditionally been used to treat cardiovascular diseases in China. In this study, we investigated if treatment with baicalein can attenuate the lung injury induced by myocardial ischemia and reperfusion (I/R). Myocardial I/R, induced by a 40-min occlusion of the left anterior descending coronary artery and a 3-h reperfusion, significantly increased histological damage and the wet-to-dry weight ratio of lungs in rats. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive nuclei and caspase-3 activation was significantly increased in the lungs. Serum and bronchoalveolar lavage fluid levels of tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]), interleukin-1[Formula: see text] (IL-1[Formula: see text]), and interleukin-6 (IL-6) were significantly elevated, as were TNF-[Formula: see text] levels in the lung. Intravenous administration with baicalein at doses of 3, 10, and 30[Formula: see text]mg/kg for ten minutes before myocardial I/R significantly reduced histological damage, the wet-to-dry weight ratio, and apoptosis in the lung. Baicalein also significantly inhibited the increase in levels of TNF-[Formula: see text], IL-1[Formula: see text], and IL-6. Moreover, baicalein increased Bcl-2 and decreased p53, Bax, and cytochrome [Formula: see text] in lungs. Phosphorylation of the prosurvival kinases, including Akt and extracellular signal-regulated kinases 1 and 2 (ERK1/2), was increased, while the phosphorylation of the pro-apoptotic mitogen-activated protein kinases, including p38 and c-Jun N-terminal kinase (JNK), was decreased. In conclusion, treatment with baicalein attenuates the lung injury induced by myocardial I/R. The mechanisms might be related to the limiting of apoptosis, possibly via the inhibition of both the extrinsic and intrinsic pathways of apoptosis, including the inhibition of TNF-[Formula: see text] production and modulation of pro- and anti-apoptotic signaling elements.

Baicalein Reduces Liver Injury Induced by Myocardial Ischemia and Reperfusion.

Baicalein is a component of the root of Scutellaria baicalensis Georgi, which has traditionally been used to treat liver disease in China. In the present study, we investigated baicalein' ability to reduce the liver injury induced by myocardial ischemia and reperfusion (I/R). Myocardial I/R was induced in this experiment by a 40[Formula: see text]min occlusion of the left anterior descending coronary artery and a 3[Formula: see text]h reperfusion in rats. The induced myocardial I/R significantly increased the serum levels of aspartate transaminase (AST) and alanine transaminase (ALT), indicating the presence of liver injury. Hepatic apoptosis was significantly increased. The serum levels of tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]), interleukin-1[Formula: see text] (IL-1[Formula: see text]), and interleukin-6 (IL-6) were significantly elevated, as was the TNF-[Formula: see text] level in the liver. Intravenous pretreatment with baicalein (3, 10, or 30[Formula: see text]mg/kg) 10[Formula: see text]min before myocardial I/R significantly reduced the serum level increase of AST and ALT, apoptosis in the liver, and the elevation of TNF-[Formula: see text], IL-1[Formula: see text], and IL-6 levels. Moreover, baicalein increased Bcl-2 and decreased Bax in the liver. Phosphorylation of the prosurvival kinases, including Akt and extracellular signal-regulated kinases 1 and 2 (ERK1/2), was also increased. In conclusion, we found that baicalein can reduce the liver injury induced by myocardial I/R. The underlying mechanisms are likely related to the inhibition of the extrinsic and intrinsic apoptotic pathways, possibly via the inhibition of TNF-[Formula: see text] production, the modulation of Bcl-2 and Bax, and the activation of Akt and ERK1/2. Our findings may provide a rationale for the application of baicalein or traditional Chinese medicine containing large amounts of baicalein to prevent liver injury in acute myocardial infarction and cardiac surgery.

Baicalein, a Component of Scutellaria baicalensis, Attenuates Kidney Injury Induced by Myocardial Ischemia and Reperfusion.

Acute kidney injury is a common and severe complication of acute myocardial infarction and cardiac surgery. It results in increased mortality, morbidity, and duration of hospitalization. Baicalein is a component of the root of Scutellaria baicalensis, which has traditionally been used to treat cardiovascular and liver diseases in Asia. In this study, we investigated whether baicalein can attenuate kidney injury induced by myocardial ischemia and reperfusion in rats. Myocardial ischemia and reperfusion, induced by a 40-minute occlusion and a 3-hour reperfusion of the left anterior descending coronary artery, significantly increased blood urea nitrogen and creatinine levels in addition to causing histological changes in the kidneys. Kidney apoptosis was also significantly increased. Furthermore, myocardial ischemia and reperfusion significantly increased the serum levels of tumor necrosis factor-α, interleukin-1, and interleukin-6 as well as the tumor necrosis factor-α levels in the kidneys. Intravenous pretreatment with baicalein (in doses of 3, 10, or 30 mg/kg), however, significantly reduced the increases in the creatinine level, renal histological damage, and apoptosis induced by myocardial ischemia and reperfusion. In addition, the increases in the serum levels of tumor necrosis factor-α, interleukin-1, and interleukin-6, and of tumor necrosis factor-α in the kidneys were significantly reduced. Western blot analysis revealed that baicalein significantly increased Bcl-2 and reduced Bax in the kidneys. The phosphorylation of Akt and extracellular signal-regulated kinases 1 and 2 was also significantly increased. In conclusion, baicalein significantly attenuates kidney injury induced by myocardial ischemia and reperfusion. The underlying mechanisms might be related to the inhibition of apoptosis, possibly through the reduction of tumor necrosis factor-α production, the modulation of Bcl-2 and Bax, and the activation of Akt and extracellular signal-regulated kinases 1 and 2.

Ischemic preconditioning activates prosurvival kinases and reduces myocardial apoptosis.

BACKGROUND: Ischemic preconditioning has been reported to protect the myocardium against ischemia and reperfusion injury. The underlying mechanisms have been extensively investigated but are not fully elucidated. In this study, we investigated the role of apoptosis in ischemic preconditioning protection and the signal pathways involved. METHODS: Myocardial ischemia and reperfusion were induced in anesthetized male Sprague-Dawley rats by a 40-minute occlusion and a 3-hour reperfusion of the left anterior descending coronary artery. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions and two 10-minute reperfusions. RESULTS: The myocardial infarct size, expressed as the percentage of area at risk, was significantly decreased in the ischemic preconditioning group (16.8 ± 2.0% and 27.9 ± 2.7% in the ischemia and reperfusion groups, respectively, p < 0.001). Additionally, ischemic preconditioning significantly reduced apoptosis, as evidenced by the decrease in the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive nuclei, DNA laddering, and caspase-3 activation. Western blot analysis revealed that ischemic preconditioning significantly reduced myocardial tumor necrosis factor-α levels. Bcl-2 was increased, whereas Bax was decreased in the myocardium. Phosphorylation of the prosurvival kinases, including Akt and extracellular signal-regulated kinases 1 and 2, was significantly increased. Hemodynamics, area at risk, and mortality did not differ significantly among the groups. CONCLUSION: Ischemic preconditioning reduces apoptosis induced by myocardial ischemia and reperfusion. The underlying mechanisms might be related to inhibition of both the extrinsic and the intrinsic apoptotic pathway via inhibition of production of tumor necrosis factor-α, modulation of expression of Bcl-2 and Bax, and activation of the prosurvival kinases.

Brief pressure overload of the left ventricle reduces myocardial infarct size via activation of protein kinase C.

BACKGROUND: We have previously reported that brief pressure overload of the left ventricle reduced myocardial infarct (MI) size. However, the role of protein kinase C (PKC) remains uncertain. In this study, we investigated whether pressure overload reduces MI size by activating PKC. METHODS: MI was induced by a 40-minute occlusion of the left anterior descending coronary artery and a 3-hour reperfusion in anesthetized Sprague-Dawley rats. MI size was determined using triphenyl tetrazolium chloride staining. Brief pressure overload was achieved by two 10-minute partial snarings of the ascending aorta, raising the systolic left ventricular pressure 50% above the baseline value. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions and 10-minute reperfusions. Dimethyl sulfoxide (vehicle) or calphostin C (0.1 mg/kg, a specific inhibitor of PKC) was administered intravenously as pretreatment. RESULTS: The MI size, expressed as the percentage of the area at risk, was significantly reduced in the pressure overload group and the ischemic preconditioning group (19.0 ± 2.9% and 18.7 ± 3.0% vs. 26.1 ± 2.6% in the control group, where p < 0.001). Pretreatment with calphostin C significantly limited the protection by pressure overload and ischemic preconditioning (25.2 ± 2.4% and 25.0 ± 2.3%, where p < 0.001). Calphostin C itself did not significantly affect MI size (25.5 ± 2.4%). Additionally, the hemodynamics, area at risk, and mortality were not significantly different. CONCLUSION: Brief pressure overload of the left ventricle reduced MI size. Since calphostin C significantly limited the decrease of MI size, our results suggested that brief pressure overload reduces MI size via activation of PKC.

Brief left ventricular pressure overload reduces myocardial apoptosis.

BACKGROUND: Both apoptosis and necrosis contribute to cell death after myocardial ischemia and reperfusion. We previously reported that brief left ventricular pressure overload (LVPO) decreased myocardial infarct (MI) size. In this study, we investigated whether brief pressure overload reduces apoptosis and the mechanisms involved. MATERIALS AND METHODS: MI was induced by a 40-min occlusion of the left anterior descending coronary artery and 3-h reperfusion in male anesthetized Sprague-Dawley rats. Brief LVPO was achieved by two 10-min partial snarings of the ascending aorta, raising the systolic left ventricular pressure 50% above the baseline value. Ischemic preconditioning was elicited by two 10-min coronary artery occlusions and 10-min reperfusions. RESULTS: Brief LVPO and ischemic preconditioning significantly decreased MI size (P < 0.001). Brief pressure overload significantly reduced myocardial apoptosis, as evidenced by the decrease in the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive nuclei (P < 0.001), little or no DNA laddering, and reduced caspase-3 activation (P < 0.01). Moreover, brief pressure overload significantly increased Bcl-2 (P < 0.001) and decreased Bax (P < 0.001) and p53 (P < 0.01). Akt phosphorylation was significantly increased by brief pressure overload (P < 0.001), whereas c-Jun N-terminal kinase phosphorylation was significantly decreased (P < 0.001). Hemodynamics, area at risk, and mortality did not differ significantly among groups. CONCLUSIONS: Brief left LVPO significantly reduces myocardial apoptosis. The underlying mechanisms might be related to modulation of Bcl-2 and Bax, inhibition of p53, increased Akt phosphorylation, and suppressed c-Jun N-terminal kinase phosphorylation.

Myocardial preconditioning reduces kidney injury and apoptosis induced by myocardial ischaemia and reperfusion.

OBJECTIVES: Acute kidney injury is a common and serious complication of cardiac surgery. Because its underlying mechanisms are unclear, there is no specific therapy to prevent or treat it. A regional transient ischaemia and reperfusion (I/R) may provide protection to distant tissue or organs, a phenomenon known as remote preconditioning. In this study, we investigated whether myocardial preconditioning (MPC) would reduce kidney injury and apoptosis induced by myocardial I/R, as well as the mechanisms involved. METHODS: Myocardial I/R was induced by a 40-min occlusion of the left anterior descending artery and a 3-h reperfusion in anaesthetized Sprague-Dawley rats. MPC was elicited by two 10-min coronary artery occlusions and two 10-min reperfusions. A sham group received the same surgical procedures without coronary artery occlusion and reperfusion. RESULTS: Compared with the sham group, myocardial I/R significantly increased the serum creatinine levels (1.15 ± 0.44 vs 0.54 ± 0.23 mg/dl, P < 0.05, mean ± standard deviation) and renal histological damage, indicating increased kidney injury. Kidney apoptosis was also significantly increased, as evidenced by the increase in the terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate (dUTP) nick-end labelling (TUNEL)-positive nuclei, clear DNA laddering and increased caspase-3 activation. Serum levels of tumour necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) were significantly elevated, as were TNF-α levels in the kidneys. MPC significantly decreased myocardial infarct size (18.5 ± 3.1 vs 25.6 ± 2.1% of area at risk, P < 0.001). Additionally, MPC significantly reduced the serum creatinine level (0.65 ± 0.19 mg/dl, P < 0.05), renal histological damage and apoptosis. The increase in the serum levels of TNF-α, IL-1 and IL-6, and of TNF-α in the kidneys, was significantly inhibited. Western blot analysis found that MPC significantly increased Bcl-2 and decreased Bax in the kidneys. Phosphorylation of Akt and extracellular signal-regulated kinases 1 and 2 (ERK1/2) was significantly increased. Haemodynamics, area at risk and mortality did not differ significantly among the groups. CONCLUSIONS: MPC significantly reduces kidney injury and apoptosis induced by myocardial I/R. The underlying mechanisms might be related to inhibition of both the extrinsic and intrinsic pathways of apoptosis, possibly via inhibition of TNF-α production, modulation of Bcl-2 and Bax and activation of Akt and ERK1/2.

The role of adenosine in preconditioning by brief pressure overload in rats.

BACKGROUND/PURPOSE: Brief pressure overload of the left ventricle reduced myocardial infarct (MI) size in rabbits has been previously reported. Its effects in other species are not known. This study investigates effects of pressure overload and the role of adenosine in rats in this study. METHODS: MI was induced by 40-minute occlusion of the left anterior descending coronary artery followed by 3-hour reperfusion. MI size was determined by triphenyl tetrazolium chloride staining. Brief pressure overload was induced by two 10-minute episodes of partial snaring of the ascending aorta. Systolic left ventricular pressure was raised 50% above the baseline value. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions. RESULTS: The MI size (mean ± standard deviation), expressed as percentage of area at risk, was significantly reduced in the pressure overload group as well as in the ischemic preconditioning group (17.4 ± 3.0% and 18.2 ± 1.5% vs. 26.6 ± 2.4% in the control group, p < 0.001). Pretreatment with 8-(p-sulfophenyl)-theophylline (SPT), an inhibitor of adenosine receptors, did not significantly limit the protection by pressure overload and ischemic preconditioning (18.3 ± 1.5% and 18.2 ± 2.0%, respectively, p < 0.001). SPT itself did not affect the extent of infarct (25.4 ± 2.0%). The hemodynamics, area at risk and mortality were not significantly different among all groups of animals. CONCLUSION: Brief pressure overload of the left ventricle preconditioned rat myocardium against infarction. Because SPT did not significantly alter MI size reduction, our results did not support a role of adenosine in preconditioning by pressure overload in rats.

Preconditioning threshold of brief pressure overload of the left ventricle.

BACKGROUND: We previously reported that pressure overload of the left ventricle reduced myocardial infarct (MI) size in rabbits. The threshold of pressure overload was investigated in this study. METHODS: Pressure overload of the left ventricle was induced by partial snare of the ascending aorta in anesthetized, open-chest rabbits. Systolic left ventricular pressure (SLVP) was elevated 50% or 30% above baseline value by varying the degree of partial snaring. Different duration of pressure overload, including 10 minutes, 5 minutes, 3 minutes, or 2 minutes, was applied to determine the threshold of protective effects. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions and reperfusions. Ten minutes after different pretreatment, 1 hour occlusion of the left anterior descending coronary artery followed by 3 hours reperfusion was done to induce MI. The size of area at risk and MI were determined by blue dye injection and triphenyl tetrazolium chloride staining after experiments. RESULTS: Pressure overload increase of SLVP 50% above baseline value for 10 minutes, 5 minutes, and 3 minutes significantly reduced MI size (18.5 ± 3.6%, 21.4 ± 1.9% and 21.6 ± 1.7%, respectively, vs. 26.6 ± 1.0% in the control group, mean ± standard deviation, p < 0.01). A 30% increase of SLVP by pressure overload for 10 minutes, 5 minutes and 3 minutes also significantly decreased MI size (20.5 ± 2.5%, 21.6 ± 2.3%, and 21.5 ± 2.3%, p < 0.01). Ischemic preconditioning significantly decreased MI size (19.9 ± 2.8%, p < 0.001). Pressure overload to elevate SLVP 50% or 30% above baseline value for 2 minutes did not significantly alter MI size (25.0 ± 2.3% and 26.0 ± 1.7%, p = 0.122 and p = 0.457). Two episodes of 2 minutes pressure overload did not significantly decrease MI size (25.0 ± 2.2% and 25.5 ± 2.2%, p = 0.118 and p = 0.281). The hemodynamics, area at risk, and mortality were not significantly different among all groups of animals. CONCLUSION: Pressure overload to raise SLVP either 50% or 30% above baseline value reduced MI size. A minimum duration of 3 minutes was necessary to induce the protective effects.

Thiazolidinediones inhibit TNF-alpha-mediated osteoclast differentiation of RAW264.7 macrophages and mouse bone marrow cells through downregulation of NFATc1.

TNF-alpha plays critical roles in bone-resorbing diseases, such as rheumatoid arthritis. Recent evidence suggests that thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor gamma agonists, have anti-inflammatory effects. The aim of this study was to evaluate the effect of TZDs on the TNF-alpha-mediated osteoclastogenesis of osteoclast precursor cells. TNF-alpha treatment of RAW264.7 murine macrophages or mouse bone marrow cells induced significant multinuclear osteoclast formation, and these differentiated osteoclast cells possessed bone-resorbing activity. The TZD drugs, rosiglitazone and pioglitazone, significantly inhibited TNF-alpha-induced osteoclast differentiation from both cell types and subsequent bone resorption. Reverse transcriptase-polymerase chain reaction, reporter gene assays, and Western blot results revealed that TZD treatment significantly suppressed NFATc1 expression. Moreover, GW9662 (a peroxisome proliferator-activated receptor gamma antagonist) prevented the inhibitory effect of TZDs on NFATc1 expression and osteoclast differentiation. In summary, our results demonstrate that TZDs inhibit TNF-alpha-mediated osteoclast differentiation by downregulation of NFATc1 expression. This observation increases the therapeutic applications of TZDs in inflammatory bone-resorbing diseases.